Human vaccines & immunotherapeutics: news

Covid-19 vaccines slow down the pandemic, dozens of candidates are in development

Vaccination for SARS-CoV-2 can curb the spread of the disease, as effectiveness data indicate. In Israel, where the majority of people have been vaccinated with two doses of BNT162b2 (Pfizer/BioNTech), vaccine effectiveness is >97% for symptomatic Covid-19 and hospitalizations, and 94% for asymptomatic disease two weeks after completing the regimen. This analysis was made at a time when the hyper-transmissible strain B.1.1.7 was dominant in the country.

Another vaccine in use, the adenovirus-vectored ChAdOx1-S (AstraZeneca), showed 76% efficacy in a large trial involving >30,000 people in the America. This trial also demonstrated safety and no increased incidence of blood clots. The vaccine had been put on hold in EU after suspicions that it may cause rare brain thrombosis. The European Medicines Agency (EMA) decided that the benefits far outweigh potential risks, and vaccination with ChAdOx1-S resumed.

The EMA has approved a fourth vaccine, the single-dose non-replicating adenovirus-based vaccine Ad26.COV2.S (J&J), for adults. EU expects 200 million doses for mass vaccination by the end of 2021.

The nanoparticle protein vaccine NVX-CoV2373 (Novavax) is close to being the next one approved after demonstrating 90% efficacy in 15,000 UK adults, with 96% and 86% efficacy for the parent and B.1.1.7 strains, respectively. In South Africa, where the lineage B.1.351 associated with increased transmissibility and viral loads predominates, the efficacy was 55%. However, no serious COVID-19 disease cases were reported following vaccination in either trial.

Vaccines are increasingly being tested for, and adapted to, emerging SARS-CoV-2 variants. The B.1.1.7 variant has been shown to increase the risk of death by 64% compared to the original strain in a UK matched-cohort study.¹

More than 80 vaccine candidates are in clinical development and more than 180 in preclinical development, according to the World Health Organization.² Additionally, antibody treatment has been shown to prevent severe illness when administered in the early stages of disease. The MAb VIR-7831 (Vir Biotechnology & GSK), whose sequence was isolated from a SARS-CoV-1 patient in 2003, as well as bamlanivimab-etesevimab combination (Eli Lilly) demonstrated ~85% efficacy in preventing hospitalization among patients with mild disease.

Checkpoint inhibitor demonstrates survival benefit in cervical cancer patients

The PD-1 inhibitor cemiplimab (Libtayo, Regeneron & Sanofi) improved overall survival in women with recurrent or metastatic squamous cell carcinoma or adenocarcinoma of the cervix. In a Phase 3 trial involving 600 subjects, those that received cemiplimab lived a median of 12 months compared to 8.5 months in the chemotherapy group.

“Libtayo monotherapy is the first medicine to demonstrate an improvement in overall survival in women with recurrent or metastatic cervical cancer following progression on platinum-based chemotherapy,” lead investigator Krishnansu Tewari of University of California, Irvine said.

The results were considered so significant that the Independent Data Monitoring Committee recommended termination of the trial and subsequent regulatory application.

Atezolizumab halted NSCLC progression in a late-stage trial

The PD-L1 inhibitor atezolizumab (Tecentriq, Genentech) extended disease-free survival in patients with stage I–III non-small cell lung cancer (NSCLC), particularly those with high PD-L1 levels. No further details of the interim analysis of the Phase 3 IMpower010 trial were disclosed.

A total of 1,000 subjects, who had undergone surgery and cisplatin chemotherapy, were randomized to receive up to 16 cycles of atezolizumab or best supportive care.

Atezolizumab has been previously approved for late-stage NSCLC and other lung cancers

Therapeutic HPV vaccine enters clinical testing

Safety and preliminary efficacy of the therapeutic HPV vaccine VTP-200 (Vaccitech) will be evaluated in a randomized, placebo-controlled Phase 1/2 trial, which is enrolling 100 women with high-risk HPV infection. VTP-200 is a CD8⁺ T cell-inducing hexavalent vaccine based on a ChAdOx-vectored prime and MVA-vectored boost.

HPV infection is responsible for nearly all cases of cervical infection, and it can lead to other tumor types in both women and men. While two prophylactic HPV vaccines are available worldwide, no therapeutic exists for chronic HPV infection.